The present invention provides a process for preparing a pure cis isomer from a mixture of cis-trans isomers of substituted benzylidene amines.
Substituted benzylidene amines of this invention, more specifically defined by formula I below, are useful intermediates in the preparation of benzamide piperidine compounds which exhibit activity as NK-1 receptor antagonists. The present synthesis of the cis isomer provides a new stereospecific pathway to the more biologically active cis benzamide piperidine in high yield.
A stereoselective route to a cis enriched benzamide piperidine was disclosed in WO 01/77100 which is U.S. patent application Ser. No. 09/811,218 filed on Mar. 16, 2001 and is incorporated herein by reference in its entirety. The resolution of the isomer enriched mixture into the desired pure isomer required additional steps accompanied by loss of valuable product. The present invention provides an alternate and more direct method for establishing the cis stereochemistry.